Faculty & Staff
Office #: FH-409
- B.S. with honors, 1967, Iowa State University
- Ph.D., 1972, Duke University
- American Cancer Society Post-Doctoral Fellow, 1972-1975, Purdue University
- Visiting Scholar, 1992, Harvard University; 2003, Northwestern University; 2006, University of Illinois at Urbana-Champaign
Our research focuses on three exciting areas of protein science. The first is the development of polymeric hemoglobins as potential blood substitutes. The second is to develop cancer-targeted photodynamic therapy agents. The third focus is to understand protein-ligand interactions through molecular dynamics simulations.
We are synthesizing polymers of hemoglobin that include antioxidant enzymes (catalase and superoxide dismutase) to be used as blood substitutes. The syntheses depend on complimentary sulfhydryl - maleimide chemistry to produce specific complexes. After we synthesize the complexes, size exclusion chromatography, oxygen binding, thermal denaturation and autoxidation experiments are done to determine the properties of the polymer. In vivo testing is done for polymers that have promising properties.
The second area of interest in the laboratory is targeted photodynamic therapy (PDT). PDT requires light, a photosensitizer and oxygen to produce singlet oxygen that can kill the cell. We are using folate to target specific cancer cell types with PDT agents. We are incorporating hemoglobin into some of the agents to increase the oxygen availability in the target cells. This approach should dramatically decrease side-effects of treatment because it features a double selectivity. Only the tumor cells will take up the PDT agent and the light is only shone on the tumor. The research is interdisciplinary and involves organic synthesis, protein chemistry, cell culture and confocal microscopy.
We are using molecular dynamics simulations to understand the interaction of proteins with ligands. Specifically, we are studying plant and bacterial globins that bind small ligands, like O2, NO and H2S, to determine the pathways for binding and escape from the heme site. We are using three computational techniques (conjugate peak refinement, locally enhanced sampling and implicit ligand sampling) to find these pathways. We study both normal and mutant proteins in collaboration with research groups around the world that do kinetic measurements on these species.
Current publications via PubMed.
Yi Gao and Kenneth W. Olsen, Unique Mechanism of Facile Polymorphic Conversion of Acetaminophen in Aqueous Medium, . Mol. Pharmaceutics, 2014, 11 (9), pp 3056–3067
Matthew S. Najor, Kenneth W. Olsen, Daniel J. Graham, and Duarte Mota de Freitas, Contribution of each Trp residue toward the intrinsic fluorescence of the Gia1 protein, Protein Science, 2014, 23(10) 1392-1402. Article first published online: 6 AUG 2014
Kyle J. Haselton, Robin David, Katherine Fell, Emily Schulte, Matthew Dybas, Kenneth W. Olsen, Stefan M. Kanzok, Molecular cloning, characterization and expression profile of a glutathione peroxidase-like thioredoxin peroxidase (TPxGl) of the rodent malaria parasite Plasmodium berghei, Parasitology International, In Press, Corrected Proof, Available online 14 March 2014
Boguslaw Nocek, Anna Starus, Magdalena Makowska-Grzyska, Blanca Gutierrez, Stephen Sanchez,Robert Jedrzejczak, Jamey C. Mack, Kenneth W. Olsen, Andrzej Joachimiak, Richard C. Holz, The Dimerization Domain in DapE Enzymes Is Required for Catalysis, PLOS ONE, May 2014, 9 (5): e93593.
Figueroa, CM, Kuhn ML, Falaschetti CA, Solamen L, Olsen KW, Ballicora, M. A. and Iglesias, A. A. (2013) Unraveling the Activation Mechanism of the Potato Tuber ADP-Glucose Pyrophosphorylase. PLoS ONE 8(6): e66824.
Y. Gao and K. W. Olsen, Molecular Dynamics of Drug Crystal Dissolution: Simulation of Acetaminophen Form I in Water, Molecular Pharmaceutics, 10:905-917 (2013).
Maxime S. Heroux, Anne D. Mohan and Kenneth W. Olsen, Ligand Migration in the Truncated-Hemoglobin of Mycobacterium tuberculosis, IUBMB Life, 63:214-220 (2011).
S. Fischer, K. W. Olsen, K. Nam, and M. Karplus, Unsuspected Pathway of the Allosteric Transition in Hemoglobin, PNAS, 108:5608-5613 (2011).
K. W. Olsen and E. Tarasov, “Cross-Linked and Polymerized Hemoglobins as Potential Blood Substitutes” in Chemistry and Biochemistry of Oxygen Therapeutics: from Transfusion to Artificial Blood, Edited by Andrea Mozzarelli and Stefano Bettati, Wiley, 2011, pp 327-344.
M. L. Kuhn, C. M. Figueroa, M. Aleanzi, K. W. Olsen, A. A. Iglesias and M. A. Ballicora. “Bi-national and interdisciplinary course in enzyme engineering.” Bioche. Mol. Biol. Educ., 38:370-379 (2010).